Notes · Ophthalmology · 9 October 2026

Retinoblastoma

Definition

• Malignant intra‑ocular tumor arising from primitive retinal cells (photoreceptor precursors).
• Most common primary ocular malignancy in children.

Epidemiology

• Incidence: 1 in 15 000–20 000 live births worldwide (~7,000 new cases/year).
• Accounts for ~3 % of all pediatric cancers.
• Slight male predominance (M : F ≈ 1.2 : 1).
• 40 % are hereditary (germ‑line RB1 mutation); 60 % are sporadic.

Aetiology

• Genetic:
  • Germ‑line mutation of the RB1 tumor‑suppressor gene on chromosome 13q14 (Knudson’s two‑hit hypothesis).
  • Autosomal dominant inheritance with high penetrance; risk of bilateral disease and second primary malignancies.
• Sporadic:
  • Two somatic RB1 mutations confined to the retina; usually unilateral, unifocal.

Pathophysiology

• Loss of RB1 function → uncontrolled proliferation of retinal progenitor cells.
• Tumor cells form flexner‑Wilmer rosettes (clusters of tumor cells surrounding a central lumen).
• Classification (International Classification of Retinoblastoma, ICRB, 2023):
  • Group A: Small tumors (<3 mm) away from fovea & optic disc.
  • Group B: Larger or closer to disc/fovea, but no subretinal fluid.
  • Group C: Localized vitreous seeding.
  • Group D: Diffuse vitreous/sub‑retinal seeding, ≥ 2 mm fluid.
  • Group E: Massive tumor, neovascular glaucoma, or extra‑ocular extension.

Clinical Features

• Leukocoria (white pupillary reflex) – most common presenting sign.
• Strabismus (due to poor vision).
• Red eye, tearing, or photophobia if tumor invades anterior segment.
• Bilateral disease: often presents earlier (median age 12 months) vs unilateral (median 24 months).
• Extra‑ocular extension: proptosis, orbital cellulitis‑like picture.

Investigations

Management (Guidelines 2024)

1. Eye‑preserving therapy (preferred for Groups A‑D)

• Chemoreduction (systemic chemotherapy):
  • Regimen: Vincristine + Carboplatin + Etoposide (VCE) – 6 cycles (3‑weekly).
  • Alternative: Carboplatin + Topotecan for high‑risk vitreous seeds.
• Focal consolidation after tumor shrinkage:
  • Laser photocoagulation (small tumors).
  • Cryotherapy (peripheral lesions).
  • Thermo‑coagulation (tumors near macula).
• Intravitreal chemotherapy (for vitreous seeds):
  • Melphalan 30 µg/0.1 ml (± topotecan).
  • Performed under strict anti‑reflux protocol (paracentesis, cryo‑seal).
• Intra‑arterial chemotherapy (IAC) (select Group B‑D):
  • Melphalan (3–7.5 mg) ± Topotecan or Carboplatin via ophthalmic artery.
  • High globe‑salvage rates (>80 % in Group D).

2. Enucleation (Group E, massive tumor, or failed eye‑preserving attempts)

• Primary enucleation for eyes with no visual potential or extra‑ocular spread.
• Orbital implant (hydroxy‑apatite) placed for cosmetic rehabilitation.

3. Adjuvant therapy (high‑risk histopathology)

• High‑risk features: post‑laminar optic nerve invasion, massive choroidal invasion, scleral/extra‑ocular extension.
• Adjuvant chemotherapy: Vincristine + Carboplatin + Etoposide for 6 cycles.
• Radiotherapy: Reserved for residual orbital disease or metastatic disease; modern conformal techniques to limit toxicity.

4. Follow‑up

• First year: every 3 months (clinical + fundus + ultrasound).
• Years 2‑5: every 6 months.
• Long‑term: annual ophthalmic exam; monitor for second malignancies (especially in germ‑line carriers).

Complications

• Local:
  • Vitreous hemorrhage, retinal detachment, cataract (post‑radiation/chemotherapy).
  • Neovascular glaucoma (Group E).
• Systemic:
  • Chemotherapy‑related neutropenia, ototoxicity (carboplatin), peripheral neuropathy (vincristine).
  • Secondary malignancies (osteosarcoma, soft‑tissue sarcoma, melanoma) – higher in germ‑line RB1 mutation carriers.
• Psychosocial: facial asymmetry after enucleation, need for prosthetic eye fitting.

High‑Yield Exam Points

• Triad: Leukocoria, strabismus, and retinal mass with calcification.
• Knudson’s two‑hit hypothesis – germ‑line vs somatic RB1 mutations.
• Bilateral disease → hereditary → need for genetic counseling.
• ICRB groups A‑E guide therapy; Group D/E often need enucleation or IAC.
• Intravitreal melphalan is the drug of choice for vitreous seeds (2023 guideline).
• High‑risk histopathology (post‑laminar optic nerve, massive choroidal invasion) mandates adjuvant chemotherapy.
• Second primary malignancies are a major cause of mortality in hereditary cases; lifelong surveillance required.
• Enucleation is curative for unilateral advanced disease; orbital implant improves cosmesis.

Practice questions

1. A 9‑month‑old infant presents with unilateral leukocoria. Fundus exam shows a 6 mm retinal mass near the ora serrata with no vitreous seeds. According to the 2023 International Classification, the tumor belongs to:
Answer: B — size >3 mm but no seeds places it in Group B.

2. Which of the following is the most appropriate adjuvant treatment for a patient with histopathology showing massive choroidal invasion after enucleation?
A) Observation only
B) External beam radiotherapy alone
C) Six cycles of Vincristine + Carboplatin + Etoposide
D) Intravitreal melphalan
Answer: C — high‑risk features require systemic chemotherapy (VCE).

3. In the management of vitreous seeds in retinoblastoma, the drug of choice for intravitreal injection is:
A) Carboplatin
B) Melphalan
C) Topotecan
D) Methotrexate
Answer: B — melphalan is the standard intravitreal agent per 2023 guidelines.

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